P-15L Bone Graft Lumbar Fusion Clinical Trial

Degenerative Disc Disease Clinical Trial

Official title:

An Assessment of P-15L Bone Graft in Transforaminal Lumbar Interbody Fusion With Instrumentation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03502057
• Other study ID #: STU00207016
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: August 2018
• Source: Northwestern University
• Contact: Surabhi Bhatt, BS
• Phone: 312-472-6024
• Email: surabhi.bhatt[@]nm.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study Design: Prospective, single-blinded, multi-center, randomized, controlled, pivotal study Study Objective: To evaluate if P-15L is not inferior in effectiveness and safety to local autologous bone (and allograft as extender where necessary) when applied in instrumented TLIF in subjects with Degenerative disc disease (DDD)

Study Endpoints:

Primary endpoint: Month 24 Composite Clinical Success (CCS):

• Achievement of fusion (Evidence of continuous trabecular bridging bone in the intervertebral space)

• At least 15-point improvement in Oswestry Disability Index (ODI)

• No new or worsening, persistent neurological deficit

• No subsequent surgical intervention at the index level

Once fusion is radiographically confirmed, it will be assumed that fusion has occurred at all subsequent time points without the need to reconfirm fusion status at later time points.

Multiplicity Controlled Secondary endpoint:

• Visit at which fusion is confirmed.

Other Secondary endpoints:

• Visual Analog Scale (VAS) pain scores, changes over time, and achievement of a 20 mm improvement (Back, left leg, right leg);

• Physical Function and Mental Health Composite Scores (Short Form Health Survey SF-12 and changes over time).

Description:

Cerapedics currently markets a peptide-enhanced bone graft product, i-FACTOR putty, for use in cervical spine degenerative disk disease. i-FACTOR putty is a composite bone substitute material consisting of the P-15 peptide adsorbed onto anorganic bone mineral and suspended in an inert biocompatible hydrogel carrier. P-15 is a synthetic, 15-amino acid peptide that mimics the cellbinding domain of Type I collagen and is able to signal a mechanical and biochemical communication pathway that ultimately results in new bone formation. The P-15 peptide enhances cell migration and induces osteoblast cell proliferation and differentiation. P-15 is specific to anchoring-dependent connective tissue mesenchymal cells, including osteogenic cells,and therefore does not induce bone formation in the absence of these cells. The receptor mediated anchorage of osteoblasts by P-15 initiates a number of signal transduction pathways that lead to the synthesis of growth factors, cytokines, and bone morphogenetic proteins.

A prospective, randomized, controlled, multi-center clinical trial in cervical spinal fusion demonstrated the safety and efficacy of i-FACTOR putty compared to standard-of-care autograft (clinicaltrials.gov NCT00310440.) The results demonstrated that i-FACTOR putty was statistically non-inferior to autograft for fusion success, improvement in Neck Disability Index (NDI) scores, neurological success and number of adverse events, at both the 1 and 2 year time point. The i-FACTOR putty was demonstrated to be statistically superior to autograft, at both 1 year and 2-years, for "overall success" which measures the patients that were successful in all of the test modalities.

Cerapedics is developing a new bone graft product formulation to enhance our product portfolio, specifically a P15-based bone graft that is appropriate for lumbar spinal fusion, called P-15L. The new formulation comprises two new materials as compared to the original i-FACTOR putty. The first is the use of porcine-derived anorganic bone mineral (ABM) as the anorganic bone matrix. The second modification is the use of bovine collagen as the inert carrier for the anorganic bone granules. The introduction of collagen as the inert carrier will allow the P-15L to be used in a TLIF surgical indication since the collagen component provides material integrity for the putty in the implant site.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 75 Years

Eligibility

Inclusion Criteria:

• Skeletally mature adults between 22 and 75 years old (inclusive);

• Back pain with radicular symptoms as evidenced by leg pain, confirmed by history and physical exam

• Radiographically determined discogenic origin of the pain demonstrating at least one of the following characteristics: Degenerated/dark disc on MRI, instability (angulation = 5° and/or translation = 3mm on flexion/extension radiographs), osteophyte formation, ligamentous thickening, decreased disc height compared to adjacent levels on radiographic film, CT, or MRI, and disc herniation on CT or MRI

• Oswestry Low Back Pain Disability Questionnaire score of = 35

• Involved disc(s) between L2 and S1

• Planned lumbar fusion at a single level only

• Failed to gain adequate relief from at least 6 months of adequate non-operative treatment;

• Able and willing to give consent to participate in study;

• Willing and able to participate in the study follow-up according to the protocol;

• Willing and able to comply with postoperative management program;

Exclusion Criteria:

• Systemic infection such as AIDS, HIV, and active hepatitis;

• Autoimmune disease

• Significant metabolic disease that in the surgeon's opinion might compromise bone growth such as osteoporosis, osteopenia, or osteomalacia

• Taking medication for the prevention of osteoporosis or other medications that may interfere with fusion (e.g. steroids, or has received drugs that interfere with bone metabolism within 2 weeks of surgery)

• Circulatory, cardiac, or pulmonary problems that could cause excessive surgical risk

• Active malignancy

• Nondiscogenic source of symptoms (e.g. tumor, etc.)

• Multiple level symptomatic degenerative disc disease

• Previous spinal instrumentation or a previous interbody fusion procedure at the involved level Isthmic Spondylolisthesis

• Spondylolisthesis = grade 2 if present

• Active local or systemic infection

• Known allergy to components within P-15L bone graft including bovine collagen

• PEEK, or materials in supplemental fixation systems

• Pregnant or planning to become pregnant in the next 2 years

• More than one level to be operated

• Has a history of substance abuse (e.g. recreational drugs, alcohol)

• Is a prisoner

• Is currently involved in a study of another investigational product for similar purpose

• Has a disease process that would preclude accurate evaluation (e.g. neuromuscular disease, significant psychiatric disease);

• Has active or recent (within the past 2 years) Worker's compensation litigation.

• Any condition that would interfere with the subject's ability to comply with the study related requirements.

Related Conditions & MeSH terms

• Back Pain
• Back Pain With Radiation
• Degenerative Disc Disease
• Intervertebral Disc Degeneration
• Radiculopathy
• Radiculopathy Lumbar

Intervention

Device:
• P-15L
P-15L is a composite bone graft material consisting of multiple components - a synthetic peptide (P-15) adsorbed onto calcium phosphate particles, which are suspended in a collagen carrier. The P-15L Bone Graft is indicated for intervertebral body fusion of the spine in skeletally mature patients. The P-15L Bone Graft is intended to be used in conjunction with a PEEK TLIF Fusion Device and posterior pedicle screw fixation cleared by the FDA for use in the lumbosacral spine.The system is to be used in patients who have had at least six months of non-operative treatment.The P-15L Bone Graft is intended for use at one level in the lumbar spine (L2-S1) for the treatment of degenerative disc disease (DDD) with up to Grade I spondylolisthesis. DDD is defined as back pain of discogenic origin with degeneration of the disc confirmed by history and radiographic studies.
• Control
Local autologous bone (mixed with an American Association of Tissue Banks (AATB) accredited cancellous allograft chip substitute when insufficient volumes of autograft are available)

Locations

Country	Name	City	State
United States	Northwestern Medicine Department of Orthopaedic Surgery	Chicago	Illinois
United States	Northwestern Medicine, Department of Orthopaedic Surgery	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	CeraPedics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achievement of fusion (Evidence of continuous trabecular bridging bone in the intervertebral space) through lumbar CT	Lumbar spine CT	24 months post-op
Primary	At least 15-point improvement in Oswestry Disability Index (ODI)	Questionnaire used to quantify disability for low back pain	24 months post-op
Primary	No subsequent surgical intervention at the index level through comprehensive examinations of revision	Revision rates	24 months post-op
Primary	No subsequent surgical intervention at the index level through comprehensive examinations of removal	Removal rates	24 months post-op
Primary	No subsequent surgical intervention at the index level through comprehensive examinations of re operation	Re-operation rates	24 months post-op
Primary	No subsequent surgical intervention at the index level through comprehensive examinations of supplemental fixation rates	Supplemental fixation rates	24 months post-op
Primary	No new or worsening, persistent neurological deficit through a clinical exam involving Knee and ankle reflex testing	Neurodynamic tests to check the mechanical movement of the neurological tissues as well as their sensitivity to mechanical stress or compression.	Neurodynamic tests to check the mechanical movement of the neurological tissues as well as their sensitivity to mechanical stress or compression.
Primary	No new or worsening, persistent neurological deficit through a clinical exam involving Straight-leg raise test	Neurodynamic tests to check the mechanical movement of the neurological tissues as well as their sensitivity to mechanical stress or compression.	24 months post-op
Primary	No new or worsening, persistent neurological deficit through a clinical exam involving Sensory and motor function assessment.	Neurodynamic tests to check the mechanical movement of the neurological tissues as well as their sensitivity to mechanical stress or compression.	Neurodynamic tests to check the mechanical movement of the neurological tissues as well as their sensitivity to mechanical stress or compression.
Secondary	Visit at which fusion is confirmed through lumbar spine CT and radiographs	Lumbar spine CT and radiographs	24 months post-op
Secondary	Visit at which fusion is confirmed through lumbar spine radiographs	Lumbar spine radiographs	24 months post-op
Secondary	Visual Analog Scale (VAS) pain scores (0-10 scale, 0 = no pain, 10 = worst pain imaginable), changes over time, and achievement of a 20mm improvement (Back, left leg, right leg)	Uni-dimensional measure of pain intensity from 0 to 10	Pre-op, 6 weeks post-op, 3 months post-op, 6 months post-op, 12 months post-op, 24 months post-op, 36 months post-op, 48 months post-op, 60 months post-op, 72 months post-op
Secondary	Physical Function Scores (12-Item Short Form Health Survey (SF-12) and changes over time); a higher SF-12 score is better.	Physical Function calculated through SF-12	Pre-op, 6 months post-op, 12 months post-op, 24 months post-op, 36 months post-op, 48 months post-op, 60 months post-op, 72 months post-op
Secondary	Mental Health Composite Scores (12-Item Short Form Health Survey (SF-12) and changes over time); a higher SF-12 score is better.	Mental Health Score calculated through SF-12	Pre-op, 6 months post-op, 12 months post-op, 24 months post-op, 36 months post-op, 48 months post-op, 60 months post-op, 72 months post-op